加拿大麦吉尔大学Lawrence Kazak研究团队揭示UCP1和CKB对冷触发脂肪细胞产热的平行控制。该研究于2024年1月24日在线发表于国际一流学术期刊《细胞—代谢》。

研究人员表示，解偶联蛋白 1（UCP1）是脂肪细胞产热的唯一介质，这是一种传统观点，主要是从遗传性缺乏Ucp1的小鼠（种系Ucp1^-/-）出生后产热减少推断出来的。然而，种系Ucp1^-/-小鼠的棕色脂肪组织存在继发性变化。

为了减轻这些可能造成混淆的辅助变化，研究人员构建了具有诱导性脂肪细胞选择性Ucp1干扰的小鼠。研究人员发现，虽然种系Ucp1^-/-小鼠会因寒冷诱导的低体温症而死亡，但大多数诱导性缺失Ucp1的小鼠在寒冷环境中仍能保持体温。然而，诱导性脂肪细胞选择性共缺失Ucp1和肌酸激酶b（Ckb，一种UCP1依赖性产热的效应物）会加剧不耐寒性。在成熟脂肪细胞中删除UCP1或UCP1/CKB共同删除后，适度的冷暴露会触发成熟棕色脂肪细胞的再生，从而协调恢复UCP1和CKB的表达。

这些研究结果表明，发热脂肪细胞利用非旁系同源蛋白冗余，即通过UCP1和CKB，来促进冷诱导的能量耗散。

附：英文原文

Title: Parallel control of cold-triggered adipocyte thermogenesis by UCP1 and CKB

Author: Janane F. Rahbani, Jakub Bunk, Damien Lagarde, Bozena Samborska, Anna Roesler, Haopeng Xiao, Abhirup Shaw, Zafir Kaiser, Jessica L. Braun, Mia S. Geromella, Val A. Fajardo, Robert A. Koza, Lawrence Kazak

Issue&Volume: 2024-01-24

Abstract: That uncoupling protein 1 (UCP1) is the sole mediator of adipocyte thermogenesis isa conventional viewpoint that has primarily been inferred from the attenuation ofthe thermogenic output of mice genetically lacking Ucp1 from birth (germline Ucp1/). However, germline Ucp1/ mice harbor secondary changes within brown adipose tissue. To mitigate these potentiallyconfounding ancillary changes, we constructed mice with inducible adipocyte-selectiveUcp1 disruption. We find that, although germline Ucp1/ mice succumb to cold-induced hypothermia with complete penetrance, most mice withthe inducible deletion of Ucp1 maintain homeothermy in the cold. However, inducible adipocyte-selective co-deletionof Ucp1 and creatine kinase b (Ckb, an effector of UCP1-independent thermogenesis) exacerbates cold intolerance. FollowingUCP1 deletion or UCP1/CKB co-deletion from mature adipocytes, moderate cold exposuretriggers the regeneration of mature brown adipocytes that coordinately restore UCP1and CKB expression. Our findings suggest that thermogenic adipocytes utilize non-paralogousprotein redundancy—through UCP1 and CKB—to promote cold-induced energy dissipation.

DOI: 10.1016/j.cmet.2024.01.001

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(24)00001-9